Latent membrane protein-1 of Epstein-Barr virus induces the expression of B-cell integration cluster, a precursor form of microRNA-155, in B lymphoma cell lines.
miR-155, a microRNA, and its precursor form, B-cell integration cluster (BIC), are involved in tumor growth. Epstein-Barr virus (EBV)-associated malignancies are categorized into three types, based on their latent gene expression pattern: latency I, II, and III. In the present study, we found that infection with EBV increased the expression of BIC; in addition, substantial expression of BIC/miR-155 was detected in latency III-, but not in latency I-type cells. In comparison, latent membrane protein-1 (LMP1) was expressed in latency III-type cells. When LMP1 was over-expressed, BIC expression increased, indicating LMP1 mediates BIC expression. LMP1 is a membrane-associated protein known to activate signaling pathways. With the use of pathway inhibitors, we found that LMP1-induced strong BIC expression, primarily through NF-kappaB and p38/MAPK pathways. These results suggest that BIC/miR-155 play a role in lymphomagenesis through NF-kappaB and p38/MAPK pathways in response to activation by EBV LMP1.
Rahadiani
Nur
N
Department of Pathology, Osaka University Graduate School of Medicine, 2-2Yamadoka, Suita, Osaka 565-0871, Japan.
Takakuwa
Tetsuya
T
Department of Human Health Science, Kyoto University Graduate School of Medicine, 53 Shogoin Kawahara-cho, Kyoto 606-8507, Japan.
Tresnasari
Kristianti
K
Department of Pathology, Osaka University Graduate School of Medicine, 2-2Yamadoka, Suita, Osaka 565-0871, Japan.
Morii
Eiichi
E
Department of Pathology, Osaka University Graduate School of Medicine, 2-2Yamadoka, Suita, Osaka 565-0871, Japan. Electronic address: morii@patho.med.osaka-u.ac.jp.
Aozasa
Katsuyuki
K
Department of Pathology, Osaka University Graduate School of Medicine, 2-2Yamadoka, Suita, Osaka 565-0871, Japan.
D001402:B-Lymphocytes / Q000378:metabolism*; D045744:Cell Line, Tumor; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000821:virology*; D035683:MicroRNAs / Q000096:biosynthesis*; D016328:NF-kappa B / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C037662:EBV-associated membrane antigen, Epstein-Barr virus; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D014763:Viral Matrix Proteins; D048051:p38 Mitogen-Activated Protein Kinases